Search

ABSTRACTWhen dealing with maintenance in the ship's engine room, the space available around machinery and systems plays an important role. A proper clearance is usually indicated by the system supplier to perform maintenance operations. This space depends on the items dimensions, the kind of intervention and on the human operator, to avoid uncomfortable or dangerous positions. However sometimes the limited space in the engine rooms (as in warships, passenger ships, research vessels) implies critical issues in complying with such ideal clearances. This work aims to develop a tool to define a relation between the maintenance costs increase and the clearance reduction, regarding a single item and/or for the whole system. This tool improves the decision-making process during the design of engine room’s layout, enabling the comparison among different solutions in terms of operational costs. The approach relies on data-driven models and Bayesian inference. The predictive tool, inserted on the Systems Engineering methodology, has been tested on a real case.

Control of mRNA translation plays a critical role in cell growth, proliferation, and differentiation and is tightly regulated by AKT and RAS oncogenic pathways. A key player in the regulation of this process is the mRNA 5′ cap-binding protein, eukaryotic translation initiation factor 4E (eIF4E). eIF4E contributes to malignancy by selectively enabling the translation of a limited pool of mRNAs that generally encode key proteins involved in cell cycle progression, angiogenesis, and metastasis. Several data indicate that the inhibition of eIF4E in tumor cell lines and xenograft models impairs tumor growth and induces apoptosis; eIF4E, therefore, can be considered a valuable target for cancer therapy. Targeting the cap-binding pocket of eIF4E should represent a way to inhibit all the eIF4E cellular functions. We present here the development and validation of different biochemical assays based on fluorescence polarization and surface plasmon resonance techniques. These assays could support high-throughput screening, further refinement, and characterization of eIF4E inhibitors, as well as selectivity assessment against CBP80/CBP20, the other major cap-binding complex of eukaryotic cells, overall providing a robust roadmap for development of eIF4E-specific inhibitors.

Background: During the last few years an increasing number of poly(ADP-ribose) polymerase (PARP) inhibitors have been appearing in the context of cancer therapy. This is mainly due to a better knowledge of the best-characterized member of the PARP family of enzymes, PARP-1, further reinforced by the recognition of the clinical benefits arising from its inhibition. Objective/method: The aim of this review is to give the reader an update on PARP inhibition in cancer therapy, by covering both the scientific (SciFinder®search) and the patent literature (Chemical Abstract®/Derwent®search) published recently (2005 – 2008). Conclusions: More patient-compliant orally available PARP-1 inhibitor clinical candidates, along with their possible use as single agents in specific, molecularly defined cancer indications, increase the expectations for this therapeutic approach. The growing understanding of the biological role of other PARPs, such as Tankyrase 1, may be of interest as new potential targets. Besides the classical NAD-mimicking pharmacophore, additional compounds, which either do not resemble nicotinamide or exploit different binding sites, are emerging.

The premature infant is more vulnerable to infection and more prone to respiratory complications than the healthy term counterparts. Secretary Immunoglobulin A (SIgA) protects againts respiratory tract infections and the secretory immune responses of premature infants to tactile stimulation were examined in this study. A pre-test/post-test counterbalanced design examined developmental effects of gentle/light systematic stroking (TAC-TIC therapy) on SIgA secretion. Unstimulated saliva was obtained from six (2M;4F) very/extrenely low birthweight (<1.2kgs), ventilated infants before and after TAC-TIC (n=14) or a control period (n=15). A one-way repeated measures ANOVA indicated that SIgA concentrations were higher (NS) after the intervention and significantly lower (DF = 1; F=4.11; p<0.05) following the control period. Based on the rationale of the 'Equilibrium Model' the intervention may be facilitating 'coactions' amongst various infant systems through self-regulatory mechanisms, and it is possibly acting as a modulator of the immune system.